Vaghela Madhuri, Iyer Krishna, Pandita Nancy
Department of Chemistry, Sunandan Divatia School of Science, SVKM's NMIMS University, Vile Parle (W), Mumbai, Maharashtra, 400056, India.
Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Santacruz (E), Kalina, Mumbai, Maharashtra, 400098, India.
Eur J Drug Metab Pharmacokinet. 2018 Apr;43(2):227-237. doi: 10.1007/s13318-017-0443-9.
Gymnema sylvestre R. Br. is a well-known Indian medicinal herb. Gymnemic acids are pentacyclic triterpenes saponins and active phytoconstituents of Gymnema sylvestre. The study aimed at evaluation of the in vitro rat liver cytochrome P450 (CYP) inhibition potential of extracts and total gymnemic acid (TA)-enriched fractions from G. sylvestre.
Standardization of G. sylvestre [ethanolic (EL), hydroethanolic (HE), total acid of ethanolic (TAE), total acid of hydroethanolic (TAHE) and total acid of aqueous (TAAQ) extract] was done with respect to deacyl gymnemic acid (DAGA), using reverse phase-high performance liquid chromatography (RP-HPLC). Total triterpenoid content was determined by vanillin perchloric acid assay.
Total triterpene content was found to be the highest in TAAQ (59.86 ± 0.005% w/w) and TAE (49.77 ± 0.009% w/w). TAAQ showed IC ≤ 50 µg/ml for all selected CYP activities. Testosterone 6β-hydroxylation was strongly inhibited by TAE (IC: 15.48 ± 2.13 µg/ml) and was moderately by TAAQ and EL with IC ≥ 50 µg/ml. Flurbiprofen 4'-hydroxylation was subject to strong, weak and moderate inhibition by TAAQ (IC: 34.67 ± 1.38 µg/ml), TAE (IC: ≥ 50 µg/ml) and EL (IC: > 50 µg/ml), respectively. Dextromethorphan O-demethylation was inhibited by TAHE and TAAQ.
In vitro inhibition studies suggested that TA strongly inhibits activity of selected CYP. This inhibition may possibly be due to triterpenoids and gymnemic acids that have been reported to be present in it. Data also suggest a potential for possible in vivo herb-drug interactions involving G. sylvestre and other medications that are metabolized by the same CYP.
匙羹藤是一种著名的印度药草。匙羹藤酸是匙羹藤中的五环三萜皂苷类活性植物成分。本研究旨在评估匙羹藤提取物及富含总匙羹藤酸（TA）的组分对大鼠肝脏细胞色素P450（CYP）的体外抑制潜力。
采用反相高效液相色谱（RP-HPLC）法，以去酰基匙羹藤酸（DAGA）为对照，对匙羹藤[乙醇提取物（EL）、氢乙醇提取物（HE）、乙醇总酸提取物（TAE）、氢乙醇总酸提取物（TAHE）和水提取物总酸（TAAQ）]进行标准化。采用香草醛高氯酸法测定总三萜含量。
发现TAAQ（59.86±0.005%w/w）和TAE（49.77±0.009%w/w）中的总三萜含量最高。TAAQ对所有选定的CYP活性均显示IC≤50μg/ml。TAE对睾酮6β-羟基化有强烈抑制作用（IC：15.48±2.13μg/ml），TAAQ和EL对其有中度抑制作用，IC≥50μg/ml。TAAQ（IC：34.67±1.38μg/ml）、TAE（IC：≥50μg/ml）和EL（IC：>50μg/ml）对氟比洛芬4'-羟基化分别有强、弱和中度抑制作用。TAHE和TAAQ抑制右美沙芬O-去甲基化。
体外抑制研究表明，TA强烈抑制选定CYP的活性。这种抑制可能是由于其中存在的三萜类化合物和匙羹藤酸。数据还表明，匙羹藤与其他经相同CYP代谢的药物之间可能存在体内药草-药物相互作用。
